1-54876242-T-G

Position:

• chr1-54876242-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000371269.9(DHCR24):​c.388-195A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,966 control chromosomes in the GnomAD database, including 21,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.51 (21052 hom., cov: 33)
• Consequence: DHCR24 ENST00000371269.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.266

Genes affected

DHCR24 (HGNC:2859): (24-dehydrocholesterol reductase) This gene encodes a flavin adenine dinucleotide (FAD)-dependent oxidoreductase which catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. The protein contains a leader sequence that directs it to the endoplasmic reticulum membrane. Missense mutations in this gene have been associated with desmosterolosis. Also, reduced expression of the gene occurs in the temporal cortex of Alzheimer disease patients and overexpression has been observed in adrenal gland cancer cells. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-54876242-T-G is Benign according to our data. Variant chr1-54876242-T-G is described in ClinVar as [Benign]. Clinvar id is 1260254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHCR24	NM_014762.4	c.388-195A>C		intron_variant		ENST00000371269.9	NP_055577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR24	ENST00000371269.9	c.388-195A>C		intron_variant		1	NM_014762.4	ENSP00000360316	P1
	ENST00000658428.1	n.235-65T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77609 AN: 151848 Hom.: 21053 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.511 AC: 77625 AN: 151966 Hom.: 21052 Cov.: 33 AF XY: 0.520 AC XY: 38629 AN XY: 74286

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.505

Alfa AF: 0.555 Hom.: 39961

Bravo AF: 0.474

Asia WGS AF: 0.515 AC: 1792 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs638944; hg19: chr1-55341915;